Transplant arteriopathy is the leading cause of long term morbidity and mortality following cardiac transplant. A rat aortic transplant model has proven a useful way of assessing the development of such arteriopathy. This model has shown that arteriopathy is a complex process involving an inflammatory cell response, smooth muscle cell migration, and smooth muscle cell proliferation. It has been hypothesized that the immune response precipitated by histocompatibility antigens induces persistent low-grade damage to the vascular endothelium, which itself secretes growth factors to repair the damage. This results in smooth muscle cell replication in the vascular wall, migration of monocytes from the media into the intima, and the development of arteriopathy. The growth factors, including platelet derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), signal via the ras-raf-ERK 1,2 pathway. The mutant G protein Gs-alpha has been shown to inhibit the ras-raf-ERK 1,2 pathway. This suggests that mutant Gs-alpha may inhibit the signaling which produces the smooth muscle proliferation seen in transplant arteriopathy. We hypothesize that G proteins play an important regulatory role in the development of transplant arteriopathy, and that Gs-alpha will inhibit transplant arteriopathy in a rat aortic transplant model.